Tuesday, June 22, 2010

Initiation of Eukaryotic Transcription IV

Changing Up the Chromatin
All of the factors that affect transcription that have been described are involved in changing the ability of RNA polymerase and transcription factors to bind to and initiate DNA transcription.   An additional method of modulating transcription is via changes to the chromatin (see writings on that here).  Histones and other proteins are able to change the packaging of DNA and, thereby, affect transcription.  The compaction of the DNA directly affects the accessibility of it to RNA polymerase and transcription factors.  Euchromatin is the active form of chromatin that is not fully compacted; in contrast heterochromatin is generally not active or accessible.  The presence of histone H1 (the linker histone, and, let’s be honest, everyone’s favorite histone) also affects the compaction of the chromatin.

How exactly do histones affect transcription?  Put simply, they prevent other proteins from binding the DNA, especially the DNA that is facing the histone core.  Further, DNA is wrapped around histones, which changes the structure of the DNA.  Such distortions can affect binding sites and preclude transcription factor binding.  If the transcription factors and RNA polymerase are to bind to the DNA, the chromatin must be unraveled and the DNA must become accessible.  One way to do this is to move the histones out of the way, opening up binding sites.  Histones are incredibly dynamic and move around on the DNA frequently, wrapping and unwrapping different sequences.  With the fluctuations of the chromatin, transcription factors can bind while the histones “breathe.”

An additional mechanism to allow access to the DNA is via histone modifications on the N-terminal domains.  The N-termini of the histones contain lysine groups that affect DNA-histone interactions.  Therefore, affecting the charged residues via acetylation or methylation, for example, will change the interactions between the histones and DNA.  Acetylation of a histone tail effectively neutralizes its charge such that its structure is altered and no longer binds DNA as tightly.  Modifications on histones can also form binding sites for transcription sites.  Chromodomains bind to methylated lysine residues, while bromodomains bind acetylated lysines.  There are a number of different modifications that affect transcription, and new effects are still being elucidated.

-          Acetylation of lysine / arginine: transcription induction
-          Phosphorylation of serine, threonine, or tyrosine: transcription induction; chromatin compaction
-          Methylation of arginine: transcription induction
-          Methylation of lysine: gene silencing
-          Ubiquitination of H2A and H2B: degradation; transcription; growth regulation
-          ADP-ribosylation: histone repelled from DNA at sites of repair

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